Induction of specific T-cell responses in HIV infection.
OBJECTIVE
To induce recovery of HIV-1-specific immune responses by combining immunization with antiviral chemotherapy.


METHODS
Forty HIV-infected patients entered a double-blind study with recombinant gp160 in combination with zidovudine or placebo. The pretreatment observation period was around 2 years and the treatment period 5 years. Eighty matched HIV-infected patients served as controls.


METHODS
Immune status was monitored by proliferation assays with HIV-specific antigens, mitogens and recall antigens. Viral load, CD4 cell counts, apoptosis, T-cell clonal analysis and CC-chemokine receptor (CCR)-5 status were determined.


RESULTS
All immunized patients showed a strong and HIV-specific T-cell proliferative response. This response was related to the immunizations, and was not enhanced by the zidovudine monochemotherapy given during the first 6 months of the immunizations. The treatments did not significantly alter viral load. Potent antiviral combination therapy given to non-immunized individuals reduced their viral load but did not influence HIV-specific immune responses. There was a trend for an increased frequency of non-progression in the immunized group compared with controls. These individuals had both wild-type and mutant CCR-5 genes.


CONCLUSIONS
The results clearly show that restoration of HIV-specific T-cell immunity occurs after immunization with the HIV gp160 antigen and is not influenced by the addition of antiviral monochemotherapy. Even intensive chemotherapy alone did not restore HIV-specific immunity and immunization alone did not influence viral load. This suggests that combinations of intensive chemotherapy with specific HIV immunization would result both in viral load reduction and improved immune responses to HIV.
Leandersson
A C
AC
Department of Virology, Swedish Institute for Infectious Disease Control, Karolinska Institute, Stockholm.
Bratt
G
G
Hinkula
J
J
Gilljam
G
G
Cochaux
P
P
Samson
M
M
Sandström
E
E
Wahren
B
B
D016915:AIDS Vaccines / Q000276:immunology / Q000627:therapeutic use*; D019380:Anti-HIV Agents / Q000627:therapeutic use; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D003131:Combined Modality Therapy; D018450:Disease Progression; D015488:HIV Antigens / Q000276:immunology; D019302:HIV Envelope Protein gp160; D015658:HIV Infections / Q000276:immunology* / Q000628:therapy / Q000821:virology; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D019713:Receptors, CCR5 / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology / Q000627:therapeutic use; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use
D016915:AIDS Vaccines; D019380:Anti-HIV Agents; D015488:HIV Antigens; D019302:HIV Envelope Protein gp160; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019713:Receptors, CCR5; D014614:Vaccines, Synthetic; C053473:VaxSyn HIV-1 (gp160) vaccine; D015215:Zidovudine